Clinically stable covid-19 patients presenting to acute unscheduled episodic care venues have increased risk of hospitalization: secondary analysis of a randomized control trial.

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial. METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive patients).We report the primary composite outcome of cardiopulmonary hospitalizations, symptomatic venous thromboembolism, myocardial infarction, stroke, transient ischemic attack, systemic arterial thromboembolism, or death among stable outpatients stratified by enrollment setting, AUEC versus MC. A propensity score for AUEC enrollment was created, and Cox proportional hazards regression with inverse probability weighting (IPW) was used to compare the primary outcome by enrollment location. RESULTS: Among the 657 ACTIV-4B patients randomized, 533 (81.1%) with known enrollment setting data were included in this analysis, 227 from AUEC settings and 306 from MC settings. In a multivariate logistic regression model, time from COVID test, age, Black race, Hispanic ethnicity, and body mass index were associated with AUEC enrollment. Irrespective of trial treatment allocation, patients enrolled at an AUEC setting were 10-times more likely to suffer from the adjudicated primary outcome, 7.9% vs. 0.7%; p < 0.001, compared with patients enrolled at a MC setting. Upon Cox regression analysis adjustment patients enrolled at an AUEC setting remained at significant risk of the primary composite outcome, HR 3.40 (95% CI 1.46, 7.94). CONCLUSIONS: Patients with clinically stable COVID-19 presenting to an AUEC enrollment setting represent a population at increased risk of arterial and venous thrombosis complications, hospitalization for cardiopulmonary events, or death, when adjusted for other risk factors, compared with patients enrolled at a MC setting. Future outpatient therapeutic trials and clinical therapeutic delivery programs of clinically stable COVID-19 patients may focus on inclusion of higher-risk patient populations from AUEC engagement locations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498273.

Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Design and rationale of the mobile health intervention for rural atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a highly morbid condition which requires long-term adherence to oral anticoagulation and may be associated with adverse quality of life and health care utilization. We developed a relational agent-an interactive smartphone-based intervention accessible regardless of digital or health literacy-to assist individuals residing in rural, Western Pennsylvania, with AF with chronic disease self-management. METHODS: The "Mobile health intervention for rural atrial fibrillation" is a single center, parallel-arm randomized clinical trial for adults with AF funded by the National Institute of Health's National Heart, Lung, and Blood Institute to enroll 264 participants. All participants receive a smartphone with data plan: The intervention is a 4 month relational agent coupled with the AliveCor Kardia for heart rate and rhythm monitoring provided by smartphone, and the control a pre-installed, smartphone-based application for health-related information (WebMD). The study uses remote recruitment and engagement to enroll individuals who would otherwise be unlikely to participate in clinical research due to rurality. The primary outcome of the trial is adherence to oral anticoagulation, determined by proportion of days covered, as measured at 12 months. The secondary outcomes are quality of life, both AF-specific and general, and health care utilization. The study entails a baseline visit, a 4 month intervention phase, and 8 and 12 month follow-up visits. CONCLUSIONS: This mobile health trial tests the effectiveness of a smartphone-based relational agent to improve clinical and patient-reported outcomes in rural-dwelling individuals.

Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial.

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.

Rurality and atrial fibrillation: a pathway to virtual engagement and clinical trial recruitment in response to COVID-19.

Study Objective: To summarize trial adaptation from in-clinic to virtual design in response to the SARS-2 coronavirus-2 (COVID-19). Design: A clinical trial of a mobile health intervention to improve chronic disease self-management for rural individuals with atrial fibrillation (AF). The trial has a 4-month intervention - accessible regardless of health or digital literacy - to enhance AF medication adherence and patient experience with 8- and 12-month assessments of sustainability. Setting: Rural, western Pennsylvania. Participants: Rural individuals with AF receiving oral anticoagulation for stroke prevention. Interventions: Enrolled participants underwent a telephone-based orientation, provided verbal consent, and were randomized using a digital platform. They received a smartphone with intervention or control applications and a curriculum on usage tailored for study arm. Participants received study assessments by mail with telephone-based administration and contact for the 12-month trial. Main Outcome Measures: Successful adaptation to virtual engagement and recruitment. Results: The study enrolled 18 participants during in-clinic recruitment (January-March 2020). From 5/1/2020 to 5/6/2021 the study team enrolled 130 individuals (median age 72.4 years, range 40.8-92.2; 49.2% women, 63.1% without college degree, and 45.4% with limited health literacy. Retention of participants enrolled using virtual methods during the 4-month intervention phase is 92%. Conclusions: We report a virtual trial of a mobile health intervention for rural individuals with AF. Our successful implementation suggests promise for engaging geographically isolated rural individuals, potential to enhance digital health access, and advance rural health equity.

The Magnet® Site Visit: Going Virtual in Response to COVID-19.

The coronavirus disease (COVID-19) pandemic has been a source of disruption, unexpected illness, stress, and adversity for people, worldwide. As the reality of the COVID-19 pandemic unfolded in early 2020, many healthcare organizations found themselves in the midst of their Magnet appraisals-just short of the 3rd appraisal phase, the Site Visit Phase. In response, the Magnet Recognition Program devised strategies to maintain the integrity of the appraisal process, despite the turbulence associated with the unexpected changes that healthcare organizations were confronting while contending with the impact of COVID-19. In this month's Magnet Perspectives column, we explore how the virtual site visit has provided healthcare organizations with the opportunity to complete this phase of their appraisal process while addressing the safety and well-being of the organization's staff as well as that of the Magnet appraisers.

Primary Care Population Management for COVID-19 Patients

Background: Most patients infected with SARS-CoV-2 have mild to moderate symptoms manageable at home;however, up to 20% develop severe illness requiring additional support. Primary care practices performing population management can use these tools to remotely assess and manage COVID-19 patients and identify those needing additional medical support before becoming critically ill. Aim: We developed an innovative population management approach for managing COVID-19 patients remotely. Setting: Development, implementation, and evaluation took place in April 2020 within a large urban academic medical center primary care practice. Participants: Our panel consists of 40,000 patients. By April 27, 2020, 305 had tested positive for SARS-CoV-2 by RT-qPCR. Outreach was performed by teams of doctors, nurse practitioners, physician assistants, and nurses. Program Description: Our innovation includes an algorithm, an EMR component, and a twice daily population report for managing COVID-19 patients remotely. Program Evaluation: Of the 305 patients with COVID-19 in our practice at time of submission, 196 had returned to baseline;54 were admitted to hospitals, six of these died, and 40 were discharged. Discussion: Our population management strategy helped us optimize at-home care for our COVID-19 patients and enabled us to identify those who require inpatient medical care in a timely fashion.

Primary Care Population Management for COVID-19 Patients.

BACKGROUND: Most patients infected with SARS-CoV-2 have mild to moderate symptoms manageable at home; however, up to 20% develop severe illness requiring additional support. Primary care practices performing population management can use these tools to remotely assess and manage COVID-19 patients and identify those needing additional medical support before becoming critically ill. AIM: We developed an innovative population management approach for managing COVID-19 patients remotely. SETTING: Development, implementation, and evaluation took place in April 2020 within a large urban academic medical center primary care practice. PARTICIPANTS: Our panel consists of 40,000 patients. By April 27, 2020, 305 had tested positive for SARS-CoV-2 by RT-qPCR. Outreach was performed by teams of doctors, nurse practitioners, physician assistants, and nurses. PROGRAM DESCRIPTION: Our innovation includes an algorithm, an EMR component, and a twice daily population report for managing COVID-19 patients remotely. PROGRAM EVALUATION: Of the 305 patients with COVID-19 in our practice at time of submission, 196 had returned to baseline; 54 were admitted to hospitals, six of these died, and 40 were discharged. DISCUSSION: Our population management strategy helped us optimize at-home care for our COVID-19 patients and enabled us to identify those who require inpatient medical care in a timely fashion.